临床荟萃 ›› 2021, Vol. 36 ›› Issue (7): 664-668.doi: 10.3969/j.issn.1004-583X.2021.07.019
收稿日期:
2021-03-06
出版日期:
2021-07-20
发布日期:
2021-08-02
通讯作者:
柴克霞
E-mail:chaikx@163.com
Received:
2021-03-06
Online:
2021-07-20
Published:
2021-08-02
摘要:
Tyro3、Axl及MerTK(TAM)受体是受体酪氨酸激酶(RTKs)的一个亚家族,通过激活配体生长停滞特异性蛋白6(Gas6)进而发挥一系列作用。TAM/Gas6通路参与并发挥多种生理学功能,且TAM/Gas6通路与多种疾病密切相关,如自身免疫性疾病、肿瘤、病毒感染及纤维化等。本文就TAM/Gas6通路的一般生物学特性及其与临床疾病的关系作一综述。
中图分类号:
吴军来, 柴克霞. TAM/Gas6通路及其与临床疾病的关系[J]. 临床荟萃, 2021, 36(7): 664-668.
[1] | Gadiyar V, Patel G, Davra V. Immunological role of TAM receptors in the cancer microenvironment[J]. Int Rev Cell Mol Biol, 2020,357:57-79. |
[2] |
Pagani S, Bellan M, Mauro D, et al. New insights into the role of Tyro3, Axl, and Mer receptors in rheumatoid arthritis[J]. Dis Markers, 2020,2020:1614627.
doi: 10.1155/2020/1614627 pmid: 32051695 |
[3] |
Nagata K, Ohashi K, Nakano T, et al. Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases[J]. J Biol Chem, 1996,271(47):30022-30027.
pmid: 8939948 |
[4] | Lew ED, Oh J, Burrola PG, et al. Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities[J]. Elife, 2014: 3. |
[5] |
Godowski PJ, Mark MR, Chen J, et al. Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3[J]. Cell, 1995,82(3):355-358.
pmid: 7634325 |
[6] |
Lemke G. Biology of the TAM receptors[J]. Cold Spring Harb Perspect Biol, 2013,5(11):a009076.
doi: 10.1101/cshperspect.a009076 URL |
[7] |
Rothlin CV, Carrera-Silva EA, Bosurgi L, et al. TAM receptor signaling in immune homeostasis[J]. Annu Rev Immunol, 2015,33:355-391.
doi: 10.1146/annurev-immunol-032414-112103 pmid: 25594431 |
[8] |
Lai C, Gore M, Lemke G. Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase[J]. Oncogene, 1994,9(9):2567-2578.
pmid: 8058320 |
[9] |
Pierce AM, Keating AK. TAM receptor tyrosine kinases: Expression, disease and oncogenesis in the central nervous system[J]. Brain Res, 2014,1542:206-220.
doi: 10.1016/j.brainres.2013.10.049 URL |
[10] |
Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells[J]. Cell, 1988,54(6):787-793.
pmid: 3409319 |
[11] |
Manfioletti G, Brancolini C, Avanzi G, et al. The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade[J]. Mol Cell Biol, 1993,13(8):4976-4985.
doi: 10.1128/mcb.13.8.4976-4985.1993 pmid: 8336730 |
[12] |
Shafit-Zagardo B, Gruber RC, DuBois JC. The role of TAM family receptors and ligands in the nervous system: From development to pathobiology[J]. Pharmacol Ther, 2018,188:97-117.
doi: 10.1016/j.pharmthera.2018.03.002 URL |
[13] |
Morioka S, Maueröder C, Ravichandran KS. Living on the edge: Efferocytosis at the interface of homeostasis and pathology[J]. Immunity, 2019,50(5):1149-1162.
doi: S1074-7613(19)30198-0 pmid: 31117011 |
[14] |
Burstyn-Cohen T, Maimon A. TAM receptors, phosphatidylserine, inflammation, and cancer[J]. Cell Commun Signal, 2019,17(1):156.
doi: 10.1186/s12964-019-0461-0 pmid: 31775787 |
[15] |
Rajotte I, Hasanbasic I, Blostein M. Gas6-mediated signaling is dependent on the engagement of its gamma-carboxyglutamic acid domain with phosphatidylserine[J]. Biochem Biophys Res Commun, 2008,376(1):70-73.
doi: 10.1016/j.bbrc.2008.08.083 URL |
[16] |
Zagórska A, Través PG, Lew ED, et al. Diversification of TAM receptor tyrosine kinase function[J]. Nat Immunol, 2014,15(10):920-928.
doi: 10.1038/ni.2986 pmid: 25194421 |
[17] |
Geng K, Kumar S, Kimani SG, et al. Requirement of gamma-carboxyglutamic acid modification and phosphatidylserine binding for the activation of Tyro3, Axl, and Mertk receptors by growth arrest-specific 6[J]. Front Immunol, 2017,8:1521.
doi: 10.3389/fimmu.2017.01521 pmid: 29176978 |
[18] |
Camenisch TD, Koller BH, Earp HS, et al. A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and lipopolysaccharide-induced endotoxic shock[J]. J Immunol, 1999,162(6):3498-3503.
pmid: 10092806 |
[19] |
Rothlin CV, Ghosh S, Zuniga EI, et al. TAM receptors are pleiotropic inhibitors of the innate immune response[J]. Cell, 2007,131(6):1124-1136.
pmid: 18083102 |
[20] |
Lu Q, Lemke G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family[J]. Science, 2001,293(5528):306-311.
pmid: 11452127 |
[21] |
Zhu H, Sun X, Zhu L, et al. Different expression patterns and clinical significance of mAxl and sAxl in systemic lupus erythematosus[J]. Lupus, 2014,23(7):624-634.
doi: 10.1177/0961203314520839 pmid: 24474706 |
[22] |
Gheita TA, Bassyouni IH, Bassyouni RH. Plasma concentrations of growth arrest specific protein 6 and the soluble form of its tyrosine kinase receptor Axl in patients with systemic lupus erythematosus and Behçets disease[J]. J Clin Immunol, 2012,32(6):1279-1286.
doi: 10.1007/s10875-012-9743-7 pmid: 22833165 |
[23] |
Wu CS, Hu CY, Tsai HF, et al. Elevated serum level of growth arrest-specific protein 6 (Gas6) in systemic lupus erythematosus patients is associated with nephritis and cutaneous vasculitis[J]. Rheumatol Int, 2014,34(5):625-629.
doi: 10.1007/s00296-013-2882-1 URL |
[24] | Cohen PL, Shao WH. Gas6/TAM receptors in systemic lupus erythematosus[J]. Dis Markers, 2019,2019:7838195. |
[25] |
Qin B, Wang J, Ma N, et al. The association of Tyro3/Axl/Mer signaling with inflammatory response, disease activity in patients with primary Sjögren's syndrome[J]. Joint Bone Spine, 2015,82(4):258-263.
doi: 10.1016/j.jbspin.2015.01.008 URL |
[26] |
Chen CH, Chen HC, Chang CC, et al. Growth arrest-specific 6 protein in patients with Sjögren syndrome: Determination of the plasma level and expression in the labial salivary gland[J]. PLoS One, 2015,10(10):e0139955.
doi: 10.1371/journal.pone.0139955 URL |
[27] |
Rothlin CV, Leighton JA, Ghosh S. Tyro3, Axl, and Mertk receptor signaling in inflammatory bowel disease and colitis-associated cancer[J]. Inflamm Bowel Dis, 2014,20(8):1472-1480.
doi: 10.1097/MIB.0000000000000050 pmid: 24846720 |
[28] |
Qin J, Li L, Zhang D, et al. Analysis of receptor tyrosine kinase genetics identifies two novel risk loci in GAS6 and PROS1 in Behçet's disease[J]. Sci Rep, 2016,6:26662.
doi: 10.1038/srep26662 URL |
[29] | Bellan M, Pirisi M, Sainaghi PP. The Gas6/TAM system and multiple sclerosis[J]. Int J Mol Sci, 2016,17(11). |
[30] |
Zhou Y, Wang Y, Chen H, et al. Immuno-oncology: Are TAM receptors in glioblastoma friends or foes[J]. Cell Commun Signal, 2021,19(1):11.
doi: 10.1186/s12964-020-00694-8 URL |
[31] |
Linger RM, Keating AK, Earp HS, et al. Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors[J]. Expert Opin Ther Targets, 2010,14(10):1073-1090.
doi: 10.1517/14728222.2010.515980 URL |
[32] | Linger RM, Keating AK, Earp HS, et al. TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer[J]. Adv Cancer Res, 2008,100:35-83. |
[33] |
Wu G, Ma Z, Cheng Y, et al. Targeting Gas6/TAM in cancer cells and tumor microenvironment[J]. Mol Cancer, 2018,17(1):20.
doi: 10.1186/s12943-018-0769-1 URL |
[34] |
Birge RB, Boeltz S, Kumar S, et al. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer[J]. Cell Death Differ, 2016,23(6):962-978.
doi: 10.1038/cdd.2016.11 pmid: 26915293 |
[35] |
Graham DK, DeRyckere D, Davies KD, et al. The TAM family: Phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer[J]. Nat Rev Cancer, 2014,14(12):769-785.
doi: 10.1038/nrc3847 URL |
[36] |
Nguyen KQ, Tsou WI, Calarese DA, et al. Overexpression of MERTK receptor tyrosine kinase in epithelial cancer cells drives efferocytosis in a gain-of-function capacity[J]. J Biol Chem, 2014,289(37):25737-25749.
doi: 10.1074/jbc.M114.570838 URL |
[37] |
Hutterer M, Knyazev P, Abate A, et al. Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme[J]. Clin Cancer Res, 2008,14(1):130-138.
doi: 10.1158/1078-0432.CCR-07-0862 pmid: 18172262 |
[38] |
Rea K, Pinciroli P, Sensi M, et al. Novel Axl-driven signaling pathway and molecular signature characterize high-grade ovarian cancer patients with poor clinical outcome[J]. Oncotarget, 2015,6(31):30859-30875.
doi: 10.18632/oncotarget.v6i31 URL |
[39] |
Myers KV, Amend SR, Pienta KJ. Targeting Tyro3, Axl and MerTK (TAM receptors): Implications for macrophages in the tumor microenvironment[J]. Mol Cancer, 2019,18(1):94.
doi: 10.1186/s12943-019-1022-2 URL |
[40] | Poon IK, Lucas CD, Rossi AG, et al. Apoptotic cell clearance: Basic biology and therapeutic potential[J]. Nat Rev Immunol, 2014,14(3):166-180. |
[41] |
Moller-Tank S, Maury W. Phosphatidylserine receptors: Enhancers of enveloped virus entry and infection[J]. Virology. 2014. 468-470:565-580.
doi: S0042-6822(14)00420-6 pmid: 25277499 |
[42] |
Vanlandschoot P, Leroux-Roels G. Viral apoptotic mimicry: An immune evasion strategy developed by the hepatitis B virus[J]. Trends Immunol, 2003,24(3):144-147.
pmid: 12615210 |
[43] |
Mercer J, Helenius A. Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells[J]. Science, 2008,320(5875):531-535.
doi: 10.1126/science.1155164 pmid: 18436786 |
[44] | Fedeli C, Torriani G, Galan-Navarro C, et al. Axl can serve as entry factor for lassa virus depending on the functional glycosylation of dystroglycan[J]. J Virol, 2018,92(5). |
[45] |
Chen J, Yang YF, Yang Y, et al. AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling[J]. Nat Microbiol, 2018,3(3):302-309.
doi: 10.1038/s41564-017-0092-4 URL |
[46] |
Brindley MA, Hunt CL, Kondratowicz AS, et al. Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein[J]. Virology, 2011,415(2):83-94.
doi: 10.1016/j.virol.2011.04.002 pmid: 21529875 |
[47] |
Meertens L, Carnec X, Lecoin MP, et al. The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry[J]. Cell Host Microbe, 2012,12(4):544-557.
doi: 10.1016/j.chom.2012.08.009 pmid: 23084921 |
[48] | Wang ZY, Wang PG, An J. The multifaceted roles of TAM receptors during Viral Infection[J]. Virol Sin, 2020:457-468. |
[49] |
Wynn TA. Cellular and molecular mechanisms of fibrosis[J]. J Pathol. 2008,214(2):199-210.
pmid: 18161745 |
[50] |
Allinovi M, De Chiara L, Angelotti ML, et al. Anti-fibrotic treatments: A review of clinical evidence[J]. Matrix Biol, 2018, 68-69:333-354.
doi: S0945-053X(17)30431-6 pmid: 29654884 |
[51] | Bellan M, Cittone MG, Tonello S, et al. Gas6/TAM system: A key modulator of the interplay between inflammation and fibrosis[J]. Int J Mol Sci, 2019,20(20). |
[52] |
Espindola MS, Habiel DM, Narayanan R, et al. Targeting of TAM receptors ameliorates fibrotic mechanisms in idiopathic pulmonary fibrosis[J]. Am J Respir Crit Care Med, 2018,197(11):1443-1456.
doi: 10.1164/rccm.201707-1519OC URL |
[53] |
Bárcena C, Stefanovic M, Tutusaus A, et al. Gas6/Axl pathway is activated in chronic liver disease and its targeting reduces fibrosis via hepatic stellate cell inactivation[J]. J Hepatol, 2015,63(3):670-678.
doi: 10.1016/j.jhep.2015.04.013 URL |
[1] | 陈思晗, 熊虎, 税典雅, 高小瞻, 刘泽伟. 超微血管成像技术诊断乳腺肿瘤的meta分析[J]. 临床荟萃, 2024, 39(2): 108-114. |
[2] | 赵旭辉, 黄小敏, 达德转, 许焱, 崔晓东, 李红玲. 基于生物信息学筛选影响胃癌患者预后的糖酵解相关基因[J]. 临床荟萃, 2024, 39(1): 20-29. |
[3] | 黄赛虎, 龙中洁, 董兴强, 孟祥营, 吴水燕, 柏振江. 血液肿瘤患儿合并脓毒血症的病原学特点及临床特征[J]. 临床荟萃, 2024, 39(1): 38-42. |
[4] | 吕畅, 周利明. TNF-α-308基因多态性与胃癌易感相关性的meta分析[J]. 临床荟萃, 2023, 38(9): 779-787. |
[5] | 武锐锋, 刘宇宏. PDZ结合激酶/T淋巴细胞因子激活的杀伤细胞源性蛋白激酶的作用机制及其在肿瘤治疗中的潜在价值[J]. 临床荟萃, 2023, 38(8): 763-768. |
[6] | 侯有玲, 李奕, 关红玉, 罗红霞. 目标导向液体治疗在脑肿瘤切除术中应用效果的meta分析[J]. 临床荟萃, 2023, 38(8): 686-693. |
[7] | 李亚, 杜涛明, 邱世香, 陈超, 钟立明. 伴有抑郁症状肝癌患者脑功能连接研究[J]. 临床荟萃, 2023, 38(6): 532-536. |
[8] | 王英南, 赵琦, 白海威, 武丹娜, 魏金梅, 李省江, 李锐凌, 张瑞星. 胃癌合并脑梗死的临床特点及危险因素分析[J]. 临床荟萃, 2023, 38(5): 417-422. |
[9] | 周腾腾, 李来有, 刘志敏, 左静. 隧道式和传统PICC穿刺法对导管相关血流感染影响的研究进展[J]. 临床荟萃, 2023, 38(5): 469-472. |
[10] | 陆知非, 王高卿, 高过. 肝门部胆管癌的非手术治疗进展[J]. 临床荟萃, 2023, 38(5): 473-476. |
[11] | 黎恒楠, 黄艳, 赵亚娟, 胡桂才. 血清CTRP5与持续非卧床腹膜透析患者左室舒张功能异常的相关性及其诊断价值[J]. 临床荟萃, 2023, 38(4): 324-329. |
[12] | 罗杰, 吴强, 李忠, 郑硕. 罕见肾上腺神经纤维瘤1例并文献复习[J]. 临床荟萃, 2023, 38(4): 359-363. |
[13] | 彭灵智, 祝成楼, 刘天祥. 超级增强子:肿瘤治疗的新靶点[J]. 临床荟萃, 2023, 38(3): 273-278. |
[14] | 祝成楼, 吴琼, 达明绪. 西格列汀治疗2型糖尿病的胰腺癌风险评估:来自随机对照试验的荟萃分析结果[J]. 临床荟萃, 2023, 38(12): 1061-1066. |
[15] | 王军宏, 高振华, 章荣龙, 姬浩民, 赵信科, 达明绪. 1980-2021年胃癌诊断文献相关质量分析——基于Web of Science 数据库的文献计量学分析[J]. 临床荟萃, 2023, 38(12): 1117-1124. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||